scholarly journals Congenital Myasthenic Syndrome Related to CHRNA1 Variant

2021 ◽  
Vol 39 (3) ◽  
pp. 219-221
Author(s):  
June Woo Ahn ◽  
Su-Keong Hwang ◽  
Jae-Hyung Kim ◽  
Hoon Jung ◽  
Jin-Sung Park
Keyword(s):  
Clinical Symptoms ◽  
Signal Transmission ◽  
Neuromuscular Disorders ◽  
Congenital Myasthenic Syndrome ◽  
Respiratory Dysfunction ◽  
Abnormal Signal ◽  
Mild Developmental Delay ◽  
The Family ◽  
Swallowing Difficulties ◽  
Myasthenic Syndrome

Congenital myasthenic syndromes are a genetically and clinically heterogeneous group of neuromuscular disorders linked by abnormal signal transmission at the motor endplate caused by various genetic defects. Major clinical symptoms include weakness and fatigue during the first years of life but patients may also present with hypotonia, facial weakness, swallowing difficulties, respiratory dysfunction, ptosis and ophthalmoparesis. Here we report a 10-year-old boy who presented with mild developmental delay and bilateral ptosis caused by a frameshift mutation in the CHRNA1 gene that co-segregated within the family, and finally diagnosed as autosomal dominant congenital myasthenic syndrome.

scholarly journals Congenital Myasthenic Syndrome Due to Compound Heterozygous Mutations in the GFPT1 Gene

2020 ◽  
Author(s):  
Yanfang Jiang ◽  
Siwen Liu ◽  
Chunyan Wang ◽  
Yan Yu ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Acetylcholinesterase Inhibitor ◽  
Neuromuscular Disorders ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Blurred Vision ◽  
Gene Encoding ◽  
Limb Weakness ◽  
Repetitive Nerve Stimulation ◽  
Muscle Action Potential ◽  
Myasthenic Syndrome

Abstract Congenital myasthenic syndrome (CMS) is a heterogeneous group of hereditary neuromuscular disorders associated with neuromuscular junction (NMJ) dysfunction. Here, we report the genetic variants and clinical follow-up of one individual suffering from CMS. The proband presented with limb weakness, and symptoms worsened after limb activities. In addition, decreases in muscle action potential were observed with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but the patient did not experience drooping eyelids or blurred vision. Trio whole exome sequencing was performed for the proband and his parents. We found two different heterozygous missense variants (c.331C>T; p.Arg111Cys and c.1428G>C; p.Lys476Asn) in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in this patient with autosomal recessive CMS, of which one was novel. The new c.1428G>C; p.Lys476Asn variant has not been previously reported, and has not been recorded in the ClinVar dataset or the gnomAD global population dataset. The phenotypes （proximal muscle weakness and fatigue while ocular and facial involvement is only minimal，limb-girdle weakness and fatigue.，beneficial and sustained response to acetylcholinesterase inhibitor treatment）of the proband were consistent with those previously reported for CMS. Our study provides important information for the diagnosis and treatment of patients with CMS.

scholarly journals Favorable outcome of COVID-19 infection in a patient with congenital myasthenic syndrome

2020 ◽  
Author(s):  
Silvia Bonanno ◽  
Lorenzo Maggi
Keyword(s):  
Muscle Weakness ◽  
Neuromuscular Disorders ◽  
Positive Outcome ◽  
Favorable Outcome ◽  
Congenital Myasthenic Syndrome ◽  
Severe Illness ◽  
First Case ◽  
Myasthenic Syndrome

Abstract Patients affected by neuromuscular disorders (NMDs) are theoretically at higher risk for severe illness from SARS-CoV2 due to respiratory and swallowing muscle weakness 1. Here we describe the first case of congenital myasthenic syndrome (CMS) who was infected with COVID-19 and showed a positive outcome.

scholarly journals A mechanism in agrin signaling revealed by a prevalent Rapsyn mutation in congenital myasthenic syndrome

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Guanglin Xing ◽  
Hongyang Jing ◽  
Lei Zhang ◽  
Yu Cao ◽  
Lei Li ◽  
...  
Keyword(s):  
Acetylcholine Receptors ◽  
Neuromuscular Disorders ◽  
E3 Ligase ◽  
Congenital Myasthenic Syndrome ◽  
Adapter Protein ◽  
Novel Approach ◽  
Myasthenic Syndrome ◽  
Self Association ◽  
Underlying Mechanisms ◽  
Mutant Genes

Neuromuscular junction is a synapse between motoneurons and skeletal muscles, where acetylcholine receptors (AChRs) are concentrated to control muscle contraction. Studies of this synapse have contributed to our understanding of synapse assembly and pathological mechanisms of neuromuscular disorders. Nevertheless, underlying mechanisms of NMJ formation was not well understood. To this end, we took a novel approach – studying mutant genes implicated in congenital myasthenic syndrome (CMS). We showed that knock-in mice carrying N88K, a prevalent CMS mutation of Rapsyn (Rapsn), died soon after birth with profound NMJ deficits. Rapsn is an adapter protein that bridges AChRs to the cytoskeleton and possesses E3 ligase activity. In investigating how N88K impairs the NMJ, we uncovered a novel signaling pathway by which Agrin-LRP4-MuSK induces tyrosine phosphorylation of Rapsn, which is required for its self-association and E3 ligase activity. Our results also provide insight into pathological mechanisms of CMS.

scholarly journals Congenital myasthenic syndrome due to compound heterozygous mutations in the GFPT1 gene

2020 ◽  
Author(s):  
Yanfang Jiang ◽  
Siwen Liu ◽  
Chunyan Wang ◽  
Yan Yu ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Acetylcholinesterase Inhibitor ◽  
Neuromuscular Disorders ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Blurred Vision ◽  
Gene Encoding ◽  
Limb Weakness ◽  
Repetitive Nerve Stimulation ◽  
Muscle Action Potential ◽  
Myasthenic Syndrome

Abstract Congenital myasthenic syndrome (CMS) is a heterogeneous group of hereditary neuromuscular disorders associated with neuromuscular junction (NMJ) dysfunction. Here, we report the genetic variants and clinical follow-up of one individual suffering from CMS. The proband presented with limb weakness, and symptoms worsened after limb activities. In addition, decreases in muscle action potential were observed with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but the patient did not experience drooping eyelids or blurred vision. Trio whole exome sequencing was performed for the proband and his parents. We found two different heterozygous missense variants (c.331C>T; p.Arg111Cys and c.1428G>C; p.Lys476Asn) in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in this patient with autosomal recessive CMS, of which one was novel. The new c.1428G>C; p.Lys476Asn variant has not been previously reported, and has not been recorded in the ClinVar dataset or the gnomAD global population dataset. The phenotypes （proximal muscle weakness and fatigue while ocular and facial involvement is only minimal，limb-girdle weakness and fatigue.，beneficial and sustained response to acetylcholinesterase inhibitor treatment）of the proband were consistent with those previously reported for CMS. Our study provides important information for the diagnosis and treatment of patients with CMS.

scholarly journals COVID-19 in a Cohort of Patients with Congenital Myasthenic Syndrome

2021 ◽  
pp. 1-3
Author(s):  
Setareh Alabaf ◽  
Karen O'Connell ◽  
Sithara Ramdas ◽  
David Beeson ◽  
Jacqueline Palace
Keyword(s):  
High Risk ◽  
Neuromuscular Transmission ◽  
Genetic Disorders ◽  
Severe Disease ◽  
Congenital Myasthenic Syndrome ◽  
Referral Centre ◽  
History Of ◽  
Myasthenic Syndrome ◽  
The Uk ◽  
Rare Group

Congenital Myasthenic Syndrome (CMS) are a rare group of genetic disorders of neuromuscular transmission. Some subtypes of CMS can be associated with respiratory and bulbar weakness and these patients may therefore be at high risk of developing a severe disease from COVID-19. We screened 73 patients with genetically confirmed CMS who were attending the UK national referral centre for evidence of previous Severe Acute Respiratory Syndrome Corona Virus 2 infection and their clinical outcome. Of 73 patients, seven had history of confirmed COVID-19. None of the infected patients developed a severe disease, and there were no signals that CMS alone carries a high risk of severe disease from COVID-19.

Combined Muscle Biopsy and Comprehensive Electrophysiology in General Anesthesia is Valuable in Diagnosis of Neuromuscular Disease in Children

2021 ◽  
Author(s):  
Christina E. Hoei-Hansen ◽  
Marie L. B. Tygesen ◽  
Morten Dunø ◽  
John Vissing ◽  
Martin Ballegaard ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Muscle Biopsy ◽  
Neuromuscular Disease ◽  
Genetic Diagnosis ◽  
Congenital Myasthenic Syndrome ◽  
Diagnostic Quality ◽  
Pathogenic Variants ◽  
Combined Use ◽  
Myasthenic Syndrome ◽  
Size Variability

Abstract Aim The diagnostic workup in patients with delayed motor milestones suspected of having either myopathy or a congenital myasthenic syndrome is complex. Our hypothesis was that performance of a muscle biopsy and neurophysiology including stimulated single-fiber electromyography during an anesthetic procedure, combined with genetic testing has a high diagnostic quality. Materials and Methods Clinical and paraclinical data were retrospectively collected from 24 patients aged from 1 month to 10 years (median: 5.2 years). Results Neurophysiology examination was performed in all patients and was abnormal in 11 of 24. No patients had findings suggestive of a myasthenic syndrome. Muscle biopsy was performed in 21 of 24 and was normal in 16. Diagnostic findings included nemaline rods, inclusion bodies, fiber size variability, and type-II fiber atrophy. Genetic testing with either a gene panel or exome sequencing was performed in 18 of 24 patients, with pathogenic variants detected in ACTA1, NEB, SELENON, GRIN2B, SCN8A, and COMP genes. Conclusion Results supporting a neuromuscular abnormality were found in 15 of 24. In six patients (25%), we confirmed a genetic diagnosis and 12 had a clinical neuromuscular diagnosis. The study suggests that combined use of neurophysiology and muscle biopsy in cases where genetic testing does not provide a diagnosis can be useful in children with delayed motor milestones and clinical evidence of a neuromuscular disease.

scholarly journals The quality of life in the relatives of Wolfram’s syndrome patients

2014 ◽  
Vol 5 (1) ◽  
pp. 89-97
Author(s):  
Gema Esteban ◽  
Mónica Ruano ◽  
Isabel Motero
Keyword(s):  
Quality Of Life ◽  
Diabetes Mellitus ◽  
Genetic Basis ◽  
Clinical Symptoms ◽  
Daily Life ◽  
Wolfram Syndrome ◽  
Clinical Aspects ◽  
The Family ◽  
Low Prevalence

Wolfram Syndrome (WS) is a rare disease (RD) with an estimated prevalence of 1/770,000 inhabitants. It is considered a multisystemic, chronic and progressive disease.WS diagnosis implies devastating consequences at physical, educational and emotional levels. WS is also known by the acronym DIDMOAD, derived from the first letters of the main clinical symptoms: Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness. Rare diseases are characterized by their low prevalence and the lack of knowledge on the pathophysiology and treatment of them. Interestingly, around 80% of RD have a genetic basis, and this fact causes doubts and uncertainties in the couples, about the idea of having another child. The existence of a RD in a family, alters significantly the relationships and the quality of life within the family. The present work remarks the huge value of psychosocial aspects in order to pay an adequate attention to these patients, not only taking care of the clinical aspects. The main purpose of this study has been to ascertain the quality of life of Wolfram’s syndrome affected patients, and its impact in the daily life.

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